Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases

Ectodysplasin A (EDA) is a member of the tumor necrosis factor (TNF) family of ligands that was initially reported to induce the formation of various ectodermal derivatives during normal prenatal development. EDA exerts its biological activity as two splice variants, namely, EDA-A1 and EDA-A2. The f...

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Main Authors: Zhensheng Cai, Xia Deng, Jue Jia, Dong Wang, Guoyue Yuan
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-12-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2021.788411/full
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author Zhensheng Cai
Xia Deng
Jue Jia
Dong Wang
Guoyue Yuan
author_facet Zhensheng Cai
Xia Deng
Jue Jia
Dong Wang
Guoyue Yuan
author_sort Zhensheng Cai
collection DOAJ
description Ectodysplasin A (EDA) is a member of the tumor necrosis factor (TNF) family of ligands that was initially reported to induce the formation of various ectodermal derivatives during normal prenatal development. EDA exerts its biological activity as two splice variants, namely, EDA-A1 and EDA-A2. The former binds to the EDA receptor (EDAR), resulting in the recruitment of the intracellular EDAR-associated death domain (EDARADD) adapter protein and the activation of the NF-κB signaling pathway, while the latter binds to a different receptor, EDA2R, also known as X-linked ectodermal dysplasia receptor (XEDAR). Inactivation mutation of the EDA gene or the genes coding for its receptors can result in hypohidrosis ectodermal dysplasia (HED), a condition that is characterized by oligotrichosis, edentulosis or oligodontia, and oligohidrosis or anhidrosis. Recently, as a new liver factor, EDA is gradually known and endowed with some new functions. EDA levels were observed to be upregulated in several metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance. In addition, EDA and its receptors have been implicated in tumor pathogenesis through the regulation of tumor cell proliferation, apoptosis, differentiation, and migration. Here, we first review the role of EDA and its two-receptor system in various signaling pathways and then discuss the physiological and pathological roles of EDA and its receptors.
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spelling doaj.art-f32b7e99ef8c49b2b3e5f39f311dbf9f2022-12-21T21:32:26ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-12-011210.3389/fphys.2021.788411788411Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple DiseasesZhensheng CaiXia DengJue JiaDong WangGuoyue YuanEctodysplasin A (EDA) is a member of the tumor necrosis factor (TNF) family of ligands that was initially reported to induce the formation of various ectodermal derivatives during normal prenatal development. EDA exerts its biological activity as two splice variants, namely, EDA-A1 and EDA-A2. The former binds to the EDA receptor (EDAR), resulting in the recruitment of the intracellular EDAR-associated death domain (EDARADD) adapter protein and the activation of the NF-κB signaling pathway, while the latter binds to a different receptor, EDA2R, also known as X-linked ectodermal dysplasia receptor (XEDAR). Inactivation mutation of the EDA gene or the genes coding for its receptors can result in hypohidrosis ectodermal dysplasia (HED), a condition that is characterized by oligotrichosis, edentulosis or oligodontia, and oligohidrosis or anhidrosis. Recently, as a new liver factor, EDA is gradually known and endowed with some new functions. EDA levels were observed to be upregulated in several metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance. In addition, EDA and its receptors have been implicated in tumor pathogenesis through the regulation of tumor cell proliferation, apoptosis, differentiation, and migration. Here, we first review the role of EDA and its two-receptor system in various signaling pathways and then discuss the physiological and pathological roles of EDA and its receptors.https://www.frontiersin.org/articles/10.3389/fphys.2021.788411/fullectodysplasin Aectodysplasin A receptorsignaling pathwaysmetabolismskeletal muscle homeostasistumorigenesis
spellingShingle Zhensheng Cai
Xia Deng
Jue Jia
Dong Wang
Guoyue Yuan
Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases
Frontiers in Physiology
ectodysplasin A
ectodysplasin A receptor
signaling pathways
metabolism
skeletal muscle homeostasis
tumorigenesis
title Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases
title_full Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases
title_fullStr Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases
title_full_unstemmed Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases
title_short Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases
title_sort ectodysplasin a ectodysplasin a receptor system and their roles in multiple diseases
topic ectodysplasin A
ectodysplasin A receptor
signaling pathways
metabolism
skeletal muscle homeostasis
tumorigenesis
url https://www.frontiersin.org/articles/10.3389/fphys.2021.788411/full
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AT juejia ectodysplasinaectodysplasinareceptorsystemandtheirrolesinmultiplediseases
AT dongwang ectodysplasinaectodysplasinareceptorsystemandtheirrolesinmultiplediseases
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